Good morning, ladies and gentlemen, and welcome to the DiaMedica Therapeutics conference call reviewing the interim phase II preeclampsia results. An audio recording of the webcast will be available shortly after the call today on DiaMedica's website at www.diamedica.com in the investor relations section. Before DiaMedica proceeds with its remarks, please note that the company will be making forward-looking statements on today's call. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these statements. More information, including factors that could cause actual results to differ from projected results, appears in the section entitled "Cautionary Note Regarding Forward-Looking Statements" in the company's press release issued today and under the heading "Risk Factors" in the company's most recent annual report on Form 10-K and the most recent quarterly report, Form 10-Q. DiaMedica's SEC filings are available on the SEC's website, www.sec.gov, and on its website, www.diamedica.com. Please also note that any comments made on today's call speak only as of today, July 17, 2025, and may no longer be accurate at the time of any replay or transcript rereading. DiaMedica disclaims any duty to update its forward-looking statements. Following the prepared remarks, the phone lines will be open for questions. I would now like to turn you over to your host for today's call, Mr. Rick Pauls, DiaMedica's President and Chief Executive Officer. Mr. Pauls. Good afternoon, everyone. Thank you for joining our call today. We're here to review the interim results from our phase II, part 1A clinical trial of DM199 for preeclampsia. These findings mark a critical milestone in our mission to transform care for hypertensive disorders of preeclampsia. I'm thrilled to be sharing with you the results that have exceeded our expectations. I'm joined today by Dr. Kathy Kloeber, the Principal Investigator for the trial. Dr. Kloeber is Professor of Maternal Fetal Medicine at Stellenbosch University, South Africa. Also joining us is David Wambek, our Chief Business Development Officer. Our Chief Medical Officer, Dr. Lorianne Masuoka, is not able to join as she is on medical leave. Preeclampsia, as many of you know, is a life-threatening disorder of high blood pressure with multi-organ damage occurring during pregnancy, often involving kidney dysfunction. The disease afflicts more than 10 million women every year globally. In the U.S., there are nearly 200,000 pregnancies annually, with the greatest need for treating in the early onset. That is within 34 weeks of pregnancy. Half of these early deliveries are driven by refractory hypertension, despite maximum blood pressure treatment. The major challenge for these mothers and their babies is that they cannot use some of the most commonly used treatments, like ACE inhibitors and ARBs, as they've been shown to cross the placental barrier and cause serious harm to the baby. Thus, we believe DM199 could offer an important safe treatment. We also announced today plans to expand into fetal growth restriction, a related disease of early pregnancy where babies are not growing as expected, which is also a huge unmet medical need with no FDA treatment options today. We believe that DM199 is uniquely positioned to address both preeclampsia and fetal growth restriction. For the data that was just announced this morning, we had set out three key objectives for the trial that have been clearly met. First and importantly, there was no placental transfer of DM199. These patients were also well tolerated with no treatment or serious adverse events. Second, we looked at blood pressure. We previously had indicated a target of a 10 millimeter or greater drop in systolic blood pressure and a 5 millimeter drop in diastolic in at least half the patients. I'm excited to report that we had a dose-dependent reduction in both systolic and diastolic. The greatest effect actually occurred in cohort nine, which was the highest dose tested. In this cohort, we had a 35 millimeter drop in systolic blood pressure and a 15 millimeter drop in diastolic at the five-minute time point. As we look further at the data, we have pooled cohorts six to nine, where we're going to be focusing our upcoming clinical trials. In these cohorts combined together, what we saw at the five-minute time point was a 25 millimeter drop in systolic and a 13 millimeter drop in diastolic. Moving to the 30-minute time point, we had a 15-point drop in systolic and 13 in the diastolic. Moving on to the 24-hour time point, we had a 20-point drop in systolic and 10 in the diastolic. As you can see from each of these time points, there's very low p-value, indicating that almost all of these patients were moving in the right direction. Third is the dilation of the intrauterine arteries. At a recent preeclampsia KOL event, it was discussed that a 10% reduction in the pulsatility index in at least half the patients would be considered clinically meaningful. As we can show here, there actually was a 13% reduction in the pulsatility index and measured blood flow resistance. This is an early sign of increasing placental perfusion and could be a future indication of disease-modifying effects of our therapy. Importantly, the study clearly met and exceeded the expectations that we had set for the trial. Dr. Kloeber, could you now take us through the study design and the demographics? I definitely can. Thank you so much, Rick. As Rick has said, the intention of this part 1A study was really to assess safety and to determine if we could find an effective dose. Because of this, we were not looking to see if we could prolong pregnancy. We specifically chose a group of women that needed to be delivered within 72 hours and had very severe preeclampsia. We wanted to make sure that the drug was safe for mums and for babies. To do this, we wanted to have a short exposure time, and we wanted to also be able to collect cord blood to make sure that DM199 didn't cross the placental barrier. The women that we included in this study were between 27 and 42 weeks pregnant, and they had very high blood pressure. They had systolic blood pressures above 150 millimeters of mercury. They were all receiving standard of care, so we didn't stop any treatments for these women. All of them already were planned to have a delivery within 72 hours. The study design was a dose escalation study design, and we wanted to play it safe. In cohort one, we started with an ultra-low dose and added a subcutaneous dose. Slowly, with three patients in each cohort, we then increased the dose until we found what we thought would be an effective dose. Next slide, please. This slide explains in a little bit more detail how we did the study. What we did is we made sure we screened all the participants, made sure that they met the eligibility criteria, then consented them and enrolled them in the trial. As soon as they were enrolled and everything was ready, we then did a baseline recording of their blood pressure, and all blood pressure recordings were done three times. They were done three times because we know blood pressures can vary, and we took a mean of the three blood pressure measurements. We also made sure that we used a blood pressure device that was validated for use in pregnancy and specifically for use in preeclampsia. We pre-specified a number of endpoints. We pre-specified blood pressure endpoints as being five minutes after we'd completed the IV infusion, half an hour after we'd completed the infusion, and 24 hours after completing the infusion. The reason why we specified these as endpoints was because they were approximately the same as the Tmax of the IV and the subcutaneous doses in healthy non-pregnant controls. We also embedded intense pharmacokinetic studies into this, and we did uterine artery Doppler studies. When we did the baseline recording before giving the drug, we also measured the blood flow in both uterine arteries and took an average. At the two-hour time point, we again repeated the uterine artery Dopplers. The patient would come in, she'd be consented. Once she was consented, we'd do the baseline recording of their blood pressures. We then start with the IV infusion of DM-199. Once the DM-199 infusion was stopped, we then take the blood pressures at five minutes, 30 minutes, and again at 24 hours for the pre-specified time points. We also recorded blood pressures at a number of other time points for safety reasons and also to have a good idea of what was happening with blood pressure variability. The subcutaneous dose was given usually one hour after completing the IV infusion dose. Next slide, please. This slide describes the baseline demographics of our participants. What you'll see here is that the median gestation at enrollment was around 37 weeks of gestation. The majority of them were at a later gestation. You can see as well that the women had very high blood pressures. The blood pressures met the criteria of the American College of Obstetrics and Gynecology's definition of severe hypertension, with systolic blood pressures of over 160 millimeters of mercury. The race of the participants was mostly Black and mixed race, and this really represents the population that we see at our preeclampsia center of excellence here in Cape Town, South Africa. The majority of women were already taking two or more antihypertensive medications before they were started on DM-199, and nearly all of the patients received magnesium sulfate. The magnesium sulfate was usually started more than 24 hours before the DM-199 was started. In this cohort, only one patient received corticosteroids, and the reason for getting the corticosteroids was because the gestational age was before 34 weeks, so it was for fetal lung maturity. Next slide, please. Before I present the delivery characteristics, I think it's always very important to provide some context. These women are not experiencing what we would consider a healthy pregnancy. They're all severely ill with a life-threatening complication of pregnancy. Some of them are sitting with systolic blood pressures above 180. Others are so swollen that they're unable to even open their eyes at times. This also makes it extremely difficult for us to site lines because they're so swollen and so edematous. It really is expected that we have a high cesarean section rate in these women because of the disease of preeclampsia. What you'll see is the cesarean section rate for these women was around 70%. These women had a planned delivery within 72 hours, so it is expected that 80% of them delivered within 24 hours. Next slide, please. Earlier I was explaining that these women are severely ill, and you can see the expected events of preeclampsia, which we actually defined in our protocol. There were some quite severe adverse or severe expected events, and these included eclampsia, HELLP syndrome, and pulmonary edema. These are really related to the pathophysiology of preeclampsia. I must say, in my experience, usually women with such severe disease, the chances of them developing these complications are much higher than what I actually saw in this study. I was pleasantly surprised that the number of women developing end-organ complications like HELLP syndrome, pulmonary edema, or even eclampsia was lower than what I was expecting. The one case of eclampsia actually occurred in a woman who was postpartum. She'd actually already been discharged and had received DM-199 more than 72 hours before she developed her eclamptic seizure. We did have some, what we call, treatment-emergent adverse events, and these included nausea, headache, and flushing. These side effects were really well tolerated. The patients expressed that they had a headache or they felt they were flushed. Usually what we did in these cases is we gave them a fluid bolus, and straight after the fluid bolus, the patients felt very well. We had no events of hypotension. No patients paused or discontinued the treatment. We had no indication that DM-199 was associated with early labor or any other complications. Next slide. I think I'm handing over to Dave now. Is that correct? This is Rick. Thank you, Dr. Kloeber. Rick, you're taking over. Okay, fantastic. Thank you. Great. This slide here shows the levels of DM-199 that were measured by cohort in both the mother and in the cord blood. After the delivery of the baby and the placenta, the cord blood was clamped on both ends and then sent into our laboratory to measure to determine if there was any DM-199 detected. Importantly, while we did not expect to see any DM-199 in the cord, we did not. This was very important for us to confirm. As we looked at initially going into the disease of preeclampsia, one of our main hypotheses is that our drug should not cross the placental barrier, which just provides a huge safety profile for this drug. What we know today is that drugs like ACE inhibitors and ARBs are contraindicated and have been shown to cause damage to the baby. As we can see here, there's a clear increase in the levels of DM-199 in the mother, but none detected in the cord blood. As I said, this was anticipated. Going to the next slide. First, when we're looking at the pre-specified time point of five minutes post-infusion, we can see here a very clear dose response curve for both the systolic and the diastolic blood pressure. Importantly, as we look at going forward, we're going to be focusing on the dose range between the six and cohort nine. We are currently waiting for the pharmacokinetics data, the PK data, so that we can really analyze that and determine where do we go next in terms of dosing. We really do see a clear effect in this range in the cohort six to nine. The greatest effect we saw was in cohort nine, as I mentioned earlier, where there was a 35 millimeters drop in systolic and 15 in the diastolic. When we combine cohort six to nine together, we see a 25 millimeters drop in systolic and 15 in the diastolic. Moving now to the next slide. At 30 minutes, we see a less steep curve as we did in the previous slide. That really has been driven by the patients in cohort nine. These three patients had an average baseline systolic blood pressure of above 180, and they were very sick. One of the learnings from this study that we'll be looking more into in future studies is that looking at potentially increasing the IV infusion for a longer period of time so we can really cool down the blood pressure while we wait for the effects of the subcutaneous dosing to kick in and start showing an effect for these patients. On slide 14, here's combining the results from cohort six to nine together. Here are just some additional time points above the pre-specified time points that we had previously shown. As you can see here, within five minutes, we can see a 25 millimeters drop. At each of these time points, I think what we were most excited about is that none of these time points did we see the systolic blood pressure go above 160. As that blood pressure does get above 160, this is when physicians are really getting worried and starting to prepare for the need for delivery. Next slide, please. Here we're looking at the same patients, but now looking at the diastolic. You can see that here we had immediately a 13 millimeter drop. We were looking for a dose that had five millimeters. The fact that we're seeing 13 and really stable throughout each of the time points, we were just thrilled to see this early data. Turning to the uterine artery resistance and the blood flow to the placenta, this is using a Doppler, and we're measuring what's called the pulsatility index. This is a measure of resistance. This was done at the two-hour time point post-infusion. As you can see here, there was a 13% average drop overall and a very low p-value. This suggests that DM199 is actually increasing placental perfusion. I think this is very important because as more blood flow gets to the placenta, this should translate into better oxygen and nutrient delivery to the fetus, which should be involved in reducing ischemia to the placental bed. With treating over several days and weeks in future studies, we would ideally anticipate seeing larger, healthier babies with prolonged gestational days and fewer neonatal events. As well, this data suggests that we're going to be moving ahead with a cohort in the ongoing study for patients with fetal growth restriction. That's being led by Dr. Kathy Kloeber. Just to summarize here, DM199 delivered very clear and statistically significant reductions in blood pressure at multiple time points that were pre-specified. There was also a dose-dependent response across the ascending cohorts. The blood pressure measurement was also important as being on target because we believe that from a mechanistic perspective, lowering blood pressure should also then be involved in helping to improve endothelial health and protection for the mothers and the babies. The enhanced placental perfusion that we're seeing is also showing some early potential signs of disease modifying. That's very encouraging. Maybe even most importantly, overall, just having a very strong safety profile and not passing the placental barrier. With these results, we feel DM199 is emerging as a potential breakthrough candidate for both preeclampsia and maybe even fetal growth restriction. As we look into what's next, there are three additional parts to the ongoing study that Dr. Kloeber is running. The part 1B is an expansion cohort to confirm the dosing and the efficacy in 30 additional patients with planned delivery. Part two, in terms of expected management arm, this is going to be early onset patients with repeated subcutaneous dosing until delivery. Part three that we're planning to also expand is with fetal growth restriction. In particular, with the dilation of the uterine arteries, we're very excited to expand into this patient population as well. With regards to fetal growth restriction, this is really a disease that's resulting from impaired blood flow to the placenta, as we can see here. There are currently no approved FDA treatments, which we see also for preeclampsia. The pulsatility index is actually one of the tools that's measured for the disease. We feel here that the ability to dilate the uterine arteries is a very strong rationale to expand into this patient cohort. With that, operator, could you please open the lines for questions? Thank you. We will now begin the question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad. If you would like to withdraw your question, simply press star one again. Your first question comes from a line of Thomas Flaten from Lake Street Capital Markets LLC. Your line is open. Hey, good afternoon. I appreciate you taking the questions. Hey, Rick, first one on the expected management grouping. Given that you saw efficacy in cohort six through nine, have you guys given any thought to maybe using multiple doses or allowing Dr. Kloeber to updose patients who she's not seeing efficacy with instead of starting at perhaps cohort nine dosing? Sure, yeah, Thomas, thank you. Excellent question. This is part of the analysis that we'll be doing over the coming weeks. We'll be looking more closely, as we look more closely at each of the cohorts, we also want to look at the PK levels, so looking at the drug profile. That's really going to help us to define where we go for dosing. One of the things that we will look at doing is the potential for titrating the dose, realizing that not every patient is the same. In particular, those patients that have higher baseline blood pressure, it's possible they may need higher dosing. That's something that'll be very important that we'll be analyzing and spending a lot of time to make sure we really narrow down in getting the dosing right. Do you know the overlap of patients with both fetal growth restriction and preeclampsia, how often those co-occur? In early onset preeclampsia, the co-occurrence is quite frequent. If you're going less than 32 weeks, it could be 50% - 75% of patients will have intrauterine growth restriction. Got it. Maybe I can add there as well. Oh, sure. I can also add that a lot of patients that present with early onset fetal growth restriction then develop preeclampsia at a later stage. The pathophysiology is definitely overlapping for some, but not all. No, that's super helpful. Thank you. Just out of curiosity, Rick, I had a couple of teeny tiny questions. Why were there four patients in cohort four? The second kind of nitpicky question was, you made a very definitive statement about there being no placental transfer, but then on the slide where you have the data, it says that the data suggests, which is not quite as definitive. I just wanted to ferret that out a little bit. I can maybe answer the four patients. That was actually one of our faults, and it ended up being a protocol violation. What we did is we draw up the dose when we give it IV. We dilute it in a saline bag. When we give the dose subcut, we draw it directly from the vial. What the study nurse did by mistake was she drew up the subcut dose from the saline bag. We under-dosed one of the participants there. We spoke with the Data Monitoring and Safety Committee, and they actually recommended that we rather include another patient at the correct dose. That's why we had four patients in that cohort. Got it. I'll answer the second part of your question, Thomas. It really had to do with the level of detection of our assay. It goes down to 0.5 nanograms per milliliter. The highest sample that we found in the maternal plasma was 5 nanograms per milliliter. We covered down to a 10x fold. Since we can't go lower than 0.5, it's always possible that there's 0.1. That's where we just can't say with 100% certainty that it's not crossing the placental barrier. If you look back a little bit, if you think about it a little bit more, our protein size is 26 kilodaltons. What passively diffuses is around 500 daltons. Drugs like low molecular weight heparin are 4 kilodaltons- 6 kilodaltons. They're given in pregnancy, and they don't cross the placental barrier. The data in totality and just the kind of the chemical profile strongly suggests that we don't cross the placental barrier. Because, again, we can't go down to zero, our limit of detection is 0.5. We just have to say it's suggestive. Super helpful, Dave. Thanks. Finally, Dr. Kloeber, since we have you on the call, I was just curious if you would share with us any anecdotal experience you had with the patients themselves. You mentioned the one patient in your prepared remarks who was very swollen. I'm just curious what you saw in actually treating these patients. I know it was a limited treatment window, but anything you could share there would be super helpful. I'm obviously a little... I'm obviously a little... I'm not blinded. It's not a placebo-controlled trial, so one has to take that into consideration. A number of the patients that were included in the trial, I was convinced that they were going to get much sicker. I was waiting for them to go into renal failure and pulmonary edema. Some of these patients actually became less swollen, sort of in front of my eyes, which is something that I don't usually see with women with such severe disease. The women also weren't complaining of symptoms that they often do complain of. Even though there were a few cases of headaches, the majority of women really felt well on this study. Many of the women were so thankful that there was a possibility that they could actually be included in this study. From my side, I feel extremely positive about the potential of DM-199. Excellent. Thanks, everyone. Your next question comes from a line of Matthew Caulfield from HC Wainwright. Your line is open. Hi guys. Great to see the interim data and thanks for taking our questions. For the treatment stage, patients receive DM-199 IV infusion. Then cohorts two through nine received subcutaneous DM-199 one hour post IV. Can you remind us of the implications for IV infusion followed by subcu delivery? Is that the intended treatment design going forward? I just had one separate follow-up. Sure, Matthew. I can take it. Yeah. As Dr. Kloeber mentioned, the purpose of this trial here is first and foremost to determine if our drug passed the placental barrier. The only way to do that is to deliver the baby and the placenta. This was proof of concept. In future studies, we are going to be looking at the expected management, where we will start off with the IV infusion. We will do subcutaneous dosing until delivery. Understood. Thanks for that. I know you mentioned exploring the PK data. Do you have any thoughts, at least at this stage, on potential dosing beyond cohort nine? I mean, based on the results we've seen so far? We're still looking at it. I think we really do want to see what that PK data looks like from safety tolerability. I think we'd be comfortable going higher, in particular on the subcutaneous. We really do want to see what that PK data looks like first before commenting any further. Got it. Very helpful and great to see the data, guys. Congrats. Great. Thank you. Your next question comes from a line of Chase Richard Knickerbocker from Craig-Hallum Capital Group LLC. Your line is open. Good afternoon. Thanks for taking our questions and congrats on the data. Maybe first, just for Dr. Kloeber, can you help us sort of establish the clinical relevance of the level of PI reduction? Is there some data sets that you hang your hat on as far as this level of reduction drove more gestational days or a healthier baby, bigger baby? Anything that you can give us from previous data sets that you're familiar with to establish that level for us? I think it's, you know, this is all very new and very novel. As Rick said, we've never had a drug before that can actually decrease the pulsatility index in the uterine artery Dopplers. It's very difficult to be able to reference data because we don't have data on a drug that does this. It's quite novel and it's quite new. What we do know is that as the pulsatility index increases in the uterine arteries, it basically shows us that there's reduced flow to the placenta and more ischemia. One would think that by increasing flow, one may be able to improve outcomes and potentially prolong pregnancy in cases of fetal growth restriction. This is very new and very exciting. Thanks. As you think about the blood pressure reduction that we saw in the studies, particularly in the higher cohorts, what interpretations do you think is fair to draw or what kind of excites you for using this drug in expected management patients? I mean, is there anything there where you kind of hang your hat on this level of systolic or diastolic reduction? Should it allow me to continue to keep this patient in expected management? I think the first thing that excited me before we started actually looking at this was the fact that we can give this as a subcut injection and that it's got such a long half-life, because that means that the woman can actually get a subcut injection and she doesn't have to repeatedly be taking tablets. Number one, the fact that it can be given as a subcut injection and it's got a relatively long half-life made me very excited. The second thing that, again, mothers are also very excited about is the fact that it's a drug that doesn't pass the placenta. If you think of all the other antihypertensive drugs, they're all small molecules, so they're all crossing the placenta and going to the baby. That's the second thing that makes me very excited about this drug. The third thing is all the other antihypertensives that we are using are really just antihypertensive drugs. They're not doing anything to the pathophysiology of preeclampsia, where DM-199 is different. DM-199 is actually improving endothelial dysfunction. I think DM-199 has much more potential than any of the other antihypertensive drugs for treating preeclampsia. Got it. Thanks. Maybe just one for you, Rick, as far as timelines. Any update on what we should expect from an enrollment perspective in 1B? How quickly do you think we can get to stage two to start getting some data in the expected management setting? Yeah, sure. Let us get back to you as we start getting those patients dosed. We really want to talk to Dr. Kathy Kloeber in terms of the timeline. I don't want to set any expectations today. I will say, though, that Dr. Kloeber really did enroll these patients rapidly, but we just don't want to set any expectations until we get the study going. In the coming months, we'll provide further updates after we have alignment on those timelines. Understood. Maybe just as far as kind of when you think it's appropriate for you to engage with the FDA around potentially a global larger phase II, phase II, phase III study here, is it kind of post the second phase here? Will you even take some of this data to them after the 1 B? How are you kind of thinking about that? Yeah, we're preparing what that'll look like here right now. We'll plan to do a submission to the FDA later this year. Understood. Thank you, guys. Great. Thank you, Chase. That concludes our question-and-answer session. I will now turn the call back over to Mr. Pauls for closing remarks. Great. We'd like to thank everybody for joining us this afternoon. In particular, I do want to thank Dr. Kloeber for joining. I know it's very late your time in South Africa today. We do believe that DM199 could become the first disease-modifying treatment for preeclampsia and for improving fetal outcomes. I just want to summarize today what we've been able to show that demonstrates importantly the safety profile of DM199 in pregnant mothers and in particular not crossing the placental barrier. We've shown some very highly statistically significant drops in systolic and diastolic blood pressure. We see these drops minutes after the IV begins, a very, very clear effect. While also showing the ability to dilate the uterine arteries, that could result in potentially one day treating the root cause of the disease of preeclampsia, that being a hypoxic placenta. We look forward to sharing further updates with you soon. Thank you again. With this, this concludes our call today. This concludes today's conference call. Thank you for your participation, and you may now disconnect.